Chemoradiotherapy for Patients With Oligometastatic Colorectal Cancer (OLGA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Universitätsklinikum Hamburg-Eppendorf
Sponsor:
Information provided by (Responsible Party):
Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier:
NCT01759238
First received: December 17, 2012
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

This study tries to evaluate the role of chemoradiation with capecitabine and bevacizumab in oligometastatic patients neither being progressive nor resectable after chemotherapy.


Condition Intervention Phase
Colorectal Cancer
Metastases
Drug: Capecitabine
Drug: Bevacizumab
Radiation: Radiotherapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Capecitabine and Bevacizumab With Radiotherapy After 3-6 Months Chemotherapy for Patients With Oligometastatic Colorectal Cancer (OLGA Trial)

Resource links provided by NLM:


Further study details as provided by Universitätsklinikum Hamburg-Eppendorf:

Primary Outcome Measures:
  • Progression free survival rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Progression free survival rate at 12 months after start of induction treatment (PFSR@12)


Secondary Outcome Measures:
  • Time to progression (TTP) in 2 cohorts [ Time Frame: 24 months ] [ Designated as safety issue: No ]

    Time to progression (TTP) in 2 cohorts:

    1. regards only progression within (TTPir) and
    2. in- and outside irradiated areas ("overall" TTP)

  • Overall Response Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Efficacy of the investigational therapy shown by the Overall Response Rate (CR and PR) according to RECIST v1.1

  • Overall survival (OS) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Quality of life (QoL) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Quality of life using the EORTC QLQ-C30 and the module CR29

  • Prognostic and predictive value of PET scan [ Time Frame: at baseline and 2 months after chemoradiation ] [ Designated as safety issue: No ]
    Prognostic and predictive value of PET scan at baseline and at 2 months after chemoradiation

  • Toxicity [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Number of adverse events, according to NCI CTCAE v4.0)


Estimated Enrollment: 72
Study Start Date: May 2013
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemoradiation
Chemoradiation with different radiotherapy regimes (depending on location and size of irradiated lesions; e.g. conventional radiotherapy with a total dose of 35 Gy, delivered in 2.5Gy fractions for 14 days or intensity-modulated and image-guided radiotherapy with a total dose of 40 Gy, delivered in 4.0 Gy fractions for 10 days or 3-8 fractions with 8-15 Gy) combined with bevacizumab (7.5mg/kg day 1) and capecitabine (825mg/m2 bid on day 1-5, 8-12 and 15-19)
Drug: Capecitabine
825mg/m2 per os bid
Other Name: Capecitabine
Drug: Bevacizumab
7.5 mg/kg
Other Name: Bevacizumab
Radiation: Radiotherapy
(conventional or intensity-modulated and image-guided radiotherapy)

Detailed Description:

Combining chemoradiation with an antiangiogenic agent has a strong biological rationale, and preclinical studies consistently show an increase in radiosensitization with combined treatment. It is well described that hypoxia or HIF-1 expression is associated with a lower radiation response and progression in solid tumors. Radiation itself induces transient tumor hypoxia, which in turn stimulates VEGF production and VEGFR-2 expression what may also serve as a paracrine proliferative stimulus that promotes out-of-field growth. The combination of radiotherapy with an antiangiogenic agent (e.g. bevacizumab) thus offers the potential to enhance the effect of radiation, and avoid further spread of disease. Furthermore, targeting tumor vasculature improves the delivery of cytotoxic drugs (e.g. capecitabine) leading to increased efficacy of chemoradiation. Combination with cytotoxic drugs could additionally limit treatment-induced hypoxia (Senan and Smit 2007; Mazeron, Anderson et al. 2011).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with histologically confirmed diagnosis of stage IV (UICC) colorectal cancer
  2. Oligometastatic disease, defined as at least one measureable lesion with size > 1cm (RECIST v1.1) to a maximum of 3 sites and 5 lesions suitable for radiotherapy according to the dose constraints for normal tissue
  3. Patients being neither progressive nor resectable after 3-6 months of first line chemotherapy (combination chemotherapy, at least chemo-doublet) with bevacizumab
  4. maximum treatment interruption after induction therapy of 6 weeks
  5. ECOG performance status ≤ 1
  6. Life expectancy > 3 months
  7. Age ≥ 18 years
  8. Haematologic function: ANC ≥ 1.5 x 109/L, platelets ≥ 75 x109/L
  9. INR < 1.5 within 7 days prior to starting study treatment. aPTT < 1.5 ULN within 7 days prior to starting study treatment
  10. adequate liver function as measured by serum transaminases (AST & ALT) ≤ 5 x ULN and a total bilirubin ≤1.5 x ULN
  11. adequate renal function: serum creatinine ≤ 1.5 x ULN
  12. signed, written informed consent
  13. ability to swallow tablets

Exclusion Criteria:

  1. treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to entering this study
  2. prior radiotherapy for metastatic lesions (prior radiotherapy for primary tumor allowed if followed by complete resection and no sign for local recurrence at the time of enrolment)
  3. Pre history or evidence upon physical/neurological examination of CNS disease (unrelated to cancer) (unless adequately treated with standard medical therapy) e.g. uncontrolled seizures
  4. fertile women (< 2 years after last menstruation) and women of childbearing potential unwilling or unable to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel or surgically sterile)
  5. pregnancy or lactation
  6. Positive serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women < 2 years after the onset of menopause. Note: a negative test has to be reconfirmed by a urine test, should the 7-day window be exceeded.
  7. Past or current history (within the last 2 years prior to treatment start) of other malignancies except metastatic colorectal cancer (patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible).
  8. Known DPD-insufficiency
  9. Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as > 4 loose stools per day)
  10. Serious, non-healing wound, ulcer or bone fracture.
  11. Evidence of bleeding diathesis or coagulopathy.
  12. Urine dipstick for proteinuria >2+. If urine dipstick is 2+, 24-hour urine must demonstrate 1 g of protein in 24 hours for patient to be eligible.
  13. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to first treatment with study medication.
  14. Clinically significant cardiovascular disease, for example CVA, myocardial infarction (£ 12 months before treatment start), unstable angina pectoris, NYHA Class II CHF, arrhythmia requiring medication, or uncontrolled hypertension.
  15. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications.
  16. Concomitant therapy with sorivudin or chemical analogues like brivudin
  17. Known hypersensitivity or contraindication to the drugs used in the trial (eg: capecitabine, bevacizumab)
  18. Inability or unwillingness to comply with the protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01759238

Locations
Germany
University Hospital Hamburg-Eppendorf Recruiting
Hamburg, Germany
Contact: A. Stein, MD    004940741056882    a.stein@uke.de   
Contact       olga@uke.de   
Sub-Investigator: A Stein, MD         
Sponsors and Collaborators
Universitätsklinikum Hamburg-Eppendorf
Investigators
Principal Investigator: Cordula Petersen, Prof. Universitätsklinikum Hamburg-Eppendorf
  More Information

No publications provided

Responsible Party: Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier: NCT01759238     History of Changes
Other Study ID Numbers: OLGA, 2011-005296-16
Study First Received: December 17, 2012
Last Updated: June 19, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Universitätsklinikum Hamburg-Eppendorf:
colorectal cancer
metastases
non resectable
chemoradiation

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Bevacizumab
Capecitabine
Fluorouracil
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 18, 2014